title: Therapeutic effects of melatonin on heatstroke-induced multiple organ dysfunction syndrome in rats.
abstract: Melatonin reportedly exerts beneficial effects to attenuate multiple organ dysfunction syndrome (MODS) in septic shock. Heatstroke resembles septic shock in many aspects. Thus, this study was performed on the anesthetized rats by using heat exposure to induce heatstroke-associated MODS. We evaluated the effect of melatonin, a versatile molecule synthesized in the pineal gland and in many organs, in heatstroke rats and showed that melatonin (0.2-5.0 mg/kg of body weight, i.v., immediately after the start of heat stress) significantly (i) attenuated hyperthermia, hypotension and hypothalamic ischemia and hypoxia, (ii) reduced plasma index of the toxic oxidizing radicals like nitric oxide metabolites and hydroxyl radicals, (iii) diminished plasma index of hepatic and renal dysfunction like creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase, (iv) attenuated plasma systemic inflammation response molecules like soluble intercellular and lesion molecule-1, E-selectin, tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6, (v) promoted plasma levels of an anti-inflammatory cytokine IL-10, (vi) reduced an index of infiltration of polymorphonuclear neutrophils in the lung like myeloperoxidase activity, and (vii) promoted the survival time to fourfold compared with the heatstroke alone group. Thus, melatonin could be a novel agent for the treatment of heatstroke animals or patients in the early stage.
authors.affiliation: Rehabilitation Department of Spinal Cord Injury, General Hospital Jinan Military, Shandong, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Lin
authors.forename: Gui-Ping
authors.initials: GP
authors.lastname: Mei
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Yi-Lei
authors.initials: YL
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Zuo
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Liu
authors.forename: Ting-Bao
authors.initials: TB
authors.lastname: Zhao
authors.forename: Mao-Tsun
authors.initials: MT
authors.lastname: Lin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D018883:Heat Stroke / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D008550:Melatonin